Independent and joint association of cord plasma pantothenate and cysteine levels with autism spectrum disorders and other neurodevelopmental disabilities in children born term and preterm.
Independent and joint association of cord plasma pantothenate and cysteine levels with autism spectrum disorders and other neurodevelopmental disabilities in children born term and preterm.
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DOI：
10.1097/pn9.0000000000000036
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发表时间：
2023-06
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泛酸（维生素 B5）是辅酶 A (CoA) 合成的前体，辅酶 A (CoA) 是数百种代谢反应的辅助因子。半胱氨酸是 CoA 合成途径中的一种氨基酸。迄今为止，关于生命早期泛酸和半胱氨酸水平在儿童神经发育障碍中的综合作用的研究还很少。研究脐带泛酸和半胱氨酸水平与足月和早产儿自闭症谱系障碍 (ASD)、注意力缺陷多动障碍 (ADHD) 和其他发育障碍 (DD) 风险之间的关系。研究样本（n = 996，其中 177 名早产儿）来自波士顿出生队列，包括 416 名神经正常儿童、87 名 ASD、269 名 ADHD 和 224 名其他 DD 儿童，这些儿童是相互排斥的。参与者在出生时就被登记，并在波士顿医学中心进行了前瞻性随访（从1998年10月1日到2018年6月30日）。出生时采集脐带血样本。使用液相色谱-串联质谱法测量血浆泛酸和半胱氨酸水平。在调整潜在的混杂因素后，较高的脐带泛酸（≥50% vs. <50%）与 ASD（调整后优势比 [aOR]：1.94，95% 置信区间 [CI]：1.06，3.55）和 ADHD（aOR：1.66，95% CI：1.14，2.40）风险较高相关。然而，单独使用脐带半胱氨酸与 ASD、ADHD 或其他 DD 的风险无关。当考虑关节关联时，与脐带泛酸水平低（<50%）和半胱氨酸水平高的儿童相比，当脐带泛酸和半胱氨酸水平升高（≥50%）时，ASD 风险更大（aOR：3.11，95% CI：1.24，7.79）。尽管早产和较高的泛酸独立地增加了 ASD 风险，但最大的风险出现在泛酸也升高（≥50%）的早产儿中，这对于所有三种结果都是如此：ASD（aOR：5.36，95％CI：2.09，13.75），ADHD（aOR：3.31，95％CI：1.78，6.16）和其他DD（aOR：3.39，95% CI：1.85，6.24）。在这个前瞻性出生队列中，我们发现较高的脐带泛酸单独存在以及与较高的半胱氨酸或早产相结合与 ASD 和 ADHD 风险增加相关。需要更多的研究来探索这种生物学上合理的途径。
Pantothenate (vitamin B5) is a precursor for coenzyme A (CoA) synthesis, which serves as a cofactor for hundreds of metabolic reactions. Cysteine is an amino acid in the CoA synthesis pathway. To date, research on the combined role of early life pantothenate and cysteine levels in childhood neurodevelopmental disabilities is scarce. To study the association between cord pantothenate and cysteine levels and risk of autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD) and other developmental disabilities (DD) in children born term and preterm. The study sample (n = 996, 177 born preterm) derived from the Boston Birth Cohort included 416 neurotypical children, 87 ASD, 269 ADHD, and 224 other DD children, who were mutually exclusive. Participants were enrolled at birth and were followed up prospectively (from October 1, 1998, to June 30, 2018) at the Boston Medical Center. Cord blood sample was collected at birth. Plasma pantothenate and cysteine levels were measured using liquid chromatography-tandem mass spectrometry. Higher cord pantothenate (≥50th percentile vs. <50th percentile) was associated with a greater risk of ASD (adjusted odds ratio [aOR]: 1.94, 95% confidence interval [CI]: 1.06, 3.55) and ADHD (aOR: 1.66, 95% CI: 1.14, 2.40), after adjusting for potential confounders. However, cord cysteine alone was not associated with risk of ASD, ADHD, or other DD. When considering the joint association, greater ASD risk was noted when both cord pantothenate and cysteine levels were elevated (≥50th percentile) (aOR: 3.11, 95% CI: 1.24, 7.79), when compared to children with low cord pantothenate (<50th percentile) and high cysteine. Even though preterm and higher pantothenate independently increased the ASD risk, the greatest risk was found in preterm children who also had elevated pantothenate (≥50th percentile), which was true for all three outcomes: ASD (aOR: 5.36, 95% CI: 2.09, 13.75), ADHD (aOR: 3.31, 95% CI: 1.78, 6.16), and other DD (aOR: 3.39, 95% CI: 1.85, 6.24). In this prospective birth cohort, we showed that higher cord pantothenate individually and in combination with higher cysteine or preterm birth were associated with increased risk of ASD and ADHD. More study is needed to explore this biologically plausible pathway.